遗传性乳腺癌中BRCA1与雌激素受体α之间的复杂关系。
The complex relationship between BRCA1 and ERalpha in hereditary breast cancer.
作者信息
Gorski Julia J, Kennedy Richard D, Hosey Alison M, Harkin D Paul
机构信息
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland.
出版信息
Clin Cancer Res. 2009 Mar 1;15(5):1514-8. doi: 10.1158/1078-0432.CCR-08-0640. Epub 2009 Feb 17.
Abstract
Breast cancer 1 (BRCA1) was initially identified as one of the genes conferring genetic predisposition to both breast and ovarian cancer. One of the interesting aspects of BRCA1-linked cancers is the observed specificity for estrogen-responsive tissues such as breast and ovary. Recent advances in our understanding of BRCA1-linked breast cancers have revealed a complex relationship between BRCA1 and estrogen receptor alpha (ERalpha) signaling. Estrogen stimulation increases expression of BRCA1 at the mRNA and protein level and conversely BRCA1 functions to both induce ERalpha mRNA expression and act as a negative regulator of ERalpha signaling. Here, we review the relationship between BRCA1 and ERalpha and discuss the use of antiestrogen therapies such as tamoxifen and aromatase inhibitors in the treatment of BRCA1 mutation carriers.
摘要
乳腺癌1（BRCA1）最初被鉴定为赋予乳腺癌和卵巢癌遗传易感性的基因之一。与BRCA1相关癌症的一个有趣方面是观察到其对雌激素反应性组织（如乳腺和卵巢）具有特异性。我们对与BRCA1相关的乳腺癌的最新认识进展揭示了BRCA1与雌激素受体α（ERα）信号传导之间的复杂关系。雌激素刺激可在mRNA和蛋白质水平上增加BRCA1的表达，相反，BRCA1的功能是诱导ERα mRNA表达并作为ERα信号传导的负调节因子。在此，我们综述BRCA1与ERα之间的关系，并讨论使用抗雌激素疗法（如他莫昔芬和芳香化酶抑制剂）治疗BRCA1突变携带者。
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